Chiral compounds are important products and intermediates in different fields of application, particularly in the field of pharma, food supplements and flavours and fragrances as different stereoisomers have strongly different properties. A very important class of chiral compounds are chiral ketones and aldehydes.
Particularly important are chiral ketones for the synthesis of aroma ingredients and for vitamins, particular for tocopherol and vitamin K1.
Natural tocopherols bear a side chain having 3 stereogenic centres of the R configuration. Synthetic routes for the synthesis of (2R,4′R,8′R)-α-tocopherol are possible starting from (R,R)-isophytol or (R,R)-phytol. However, as natural sources of (2R,4′R,8′R)-tocopherols and (R,R)-phytol, are very limited, the market has a strong need for an effective synthesis of (2R,4′R,8′R)-tocopherols and (R,R)-isophytol, respectively, and chiral ketones or aldehydes are important intermediates for their synthesis.
It is known that chiral ketones are accessible from asymmetric hydrogenation of unsaturated ketones using chiral transition metal complexes. An important class of chiral transition metal complexes are chiral iridium complexes.
For example WO 2006/066863 A1 discloses a specific class of chiral iridium complexes which are suitable for the asymmetric hydrogenation of alkenes showing high stereoselectivity in the formation of hydrogenated ketones at high conversion. However, the iridium complexes need to be used in a relatively high amount relative to the unsaturated compounds to be hydrogenated. Due to the high price of iridium complexes it is commercially interesting to use as little iridium complex as possible while maintaining high conversion and good stereoselectivity.